Non-Alcoholic Steatohepatitis
Conditions
Keywords
NASH, Non-Alcoholic Steatohepatitis (NASH)
Brief summary
A randomized, double-blind study to assess the safety, tolerability, PK and efficacy of EDP-305 in subjects with Non-Alcoholic Steatohepatitis
Interventions
DRUGEDP-305 Dose 1
Two tablets daily for 12 weeks
DRUGEDP-305 Dose 2
Two tablets daily for 12 weeks
DRUGPlacebo
Two tablets daily for 12 weeks
Sponsors
ICON Clinical Research
Triangle Biostatistics, LLC
Enanta Pharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* An informed consent document must be signed and dated by the subject * Male and female subjects of any ethnic origin between the ages of 18 and 75 years, inclusive * Male or female with presence of NASH by: * Histologic evidence on a historical liver biopsy within 24 months of Screening consistent with NASH with fibrosis (no cirrhosis), and elevated ALT at Screening AND Screening MRI PDFF with \>8 % steatosis OR * Phenotypic diagnosis of NASH based on elevated ALT and diagnosis of T2DM or pre-diabetes AND Screening MRI PDFF with \>8 % steatosis * Body mass index (BMI) \>25 kg/m2; for Asian-Americans, BMI \>23 kg/m2 * Female subjects of childbearing potential must agree to use two effective methods of contraception from the date of Screening until 90 days after the last dose of EDP-305. * Subject must be willing and able to adhere to the assessments, visit schedules, prohibitions and restrictions, as described in this protocol
Exclusion criteria
* Laboratory Screening Results: * Total bilirubin \> ULN (normal range 0.2-1.2 mg/dL) * Total white blood cells (WBC) \<3,000 cells/mm3 * Absolute neutrophil count (ANC) \<1,500 cells/mm3 * Platelet count \<140,000/mm3 * Prothrombin time (international normalized ratio, INR) \> 1.2 * Creatine kinase above the upper limit of normal (ULN) except when in relation with intense exercise * Serum creatinine \>2 mg/dL or creatinine clearance \<60 ml/min (based on Cockroft Gault method) * Known history of alpha-1-antitrypsin deficiency * Use of an experimental treatment for NASH within the past 6 months * Use of immunosuppressant (eg, corticosteroids) for more than 2 weeks in duration within 1 year prior to Screening and during the course of the study * Use of experimental or unapproved drugs within a year of Screening * Any other condition(s) (including cardiovascular diseases) that would compromise the safety of the subject or compromise the quality of the clinical study, as judged by the Principal Investigator (PI) * Pregnant or nursing females * Recipients of liver or other organ transplantation or anticipated need for orthotropic organ transplantation in one year as determined by a Model for End-Stage Liver Disease (MELD) Score ≥ 15 * Clinical suspicion of advanced liver disease or cirrhosis * Coexisting liver or biliary diseases, such as primary sclerosing cholangitis (PSC), choledocholithiasis, acute or chronic hepatitis, autoimmune hepatitis, alcoholic liver disease, acute infection of bile duct system or gall bladder, history of gastrointestinal bleeding (secondary to portal hypertension), cirrhosis * Suspicion of cancer (eg, liver cancer) with the exception of basal cell carcinoma that has been resected * Cirrhosis with or without complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma, bilirubin \> 2xULN * Hepatorenal syndrome (type I or II) or Screening serum creatinine \> 2 mg/dL (178 μmol/L) * Prior variceal hemorrhage, uncontrolled encephalopathy, Child-Pugh Class A, B, and C, esophageal varices, or refractory ascites within the previous 6 months of Screening (defined as date informed consent signed) * Any condition possibly affecting drug absorption (eg, gastrectomy \<3 years prior to Screening) * Subject has received an investigational agent or vaccine within 30 days, or a biological product within 3 months or 5 elimination half-lives (whichever is longer) prior to the planned intake of study drug. NOTE: Flu vaccine will be allowed upon Medical Monitor's approval * Use of a new statin regimen from Screening and throughout study duration. NOTE: Subjects on a stable dose of statins for at least three months prior to Screening are allowed. No dose modification during the study will be allowed. * Current use of fibrates. Note: Subjects who discontinued fibrates for at least 3 months before Screening can participate * Clinically significant history of drug sensitivity or allergy, as determined by the PI * Uncontrolled diabetes mellitus (ie, HbA1c ≥9% or higher) 60 days prior to Day 1 * Subjects with contraindications to MRI imaging, or not being able to have the MRI performed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline (Average) in Alanine Aminotransferase (ALT) at Week 12 | Baseline and Week 12 | Blood samples were collected at specific timepoints for the laboratory evaluation to assess the ALT level. Baseline refers to the average of the screening and the Day 1 values; if either the screening or Day 1 values were missing, the non-missing value was used. Mean change was defined as the mean value at Week 12 minus the mean value at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Homeostasis Model Assessment (HOMA) Index for Nondiabetic Participants at Week 12 | Baseline and Week 12 | Blood samples were collected at specific timepoints for the laboratory evaluation; from the results of fasting glucose and insulin, an insulin resistance (IR) was estimated for the nondiabetic participants using the HOMA-IR computer algorithm. A higher HOMA-IR indicates a higher degree of insulin resistance. Participants who were not considered as having type 2 diabetes mellitus (T2DM) were identified as nondiabetic. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline. |
| Mean Change From Baseline in Aspartate Aminotransferase to Platelet Ratio Index (APRI) at Week 12 | Baseline and Week 12 | Blood samples were collected at specific timepoints for the laboratory evaluation to assess the aspartate aminotransferase (AST) level and platelet count. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. The APRI score (AST to platelet ratio index) is an index comprised of biochemical values and is used to determine the degree of hepatic fibrosis. APRI is calculated from the level of AST measured in a blood test (international units per liter \[IU/L\]) and platelet count (10\^9/L) according to the following formula: APRI = (\[AST value in IU/L / upper limit of the normal range of AST\] / \[platelet count in 10\^9/L\]) × 100. In general, APRI scores range from 0 to \>2.0, where scores \<0.5 indicate no significant fibrosis, scores \>1.5 indicate significant fibrosis, and scores \>2.0 have been shown to be best correlated with the presence of cirrhosis. Mean change was defined as the mean value at Week 12 minus the mean value at baseline. |
| Mean Change From Baseline in Triglycerides (TG) at Week 12 | Baseline and Week 12 | Blood samples were collected at specific timepoints for the laboratory evaluation to assess the TG level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline. |
| Mean Change From Baseline in Total Cholesterol at Week 12 | Baseline and Week 12 | Blood samples were collected at specific timepoints for the laboratory evaluation to assess the total cholesterol level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline. |
| Mean Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12 | Baseline and Week 12 | Blood samples were collected at specific timepoints for the laboratory evaluation to assess the HDL-C level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline. |
| Mean Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | Baseline and Week 12 | Blood samples were collected at specific timepoints for the laboratory evaluation to assess the LDL-C level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline. |
| Mean Change From Baseline in Adiponectin at Week 12 | Baseline and Week 12 | Blood samples were collected at specific timepoints for the laboratory evaluation to assess the adiponectin level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline. |
| Mean Change From Baseline in Apolipoproteins A1 (ApoA-1) at Week 12 | Baseline and Week 12 | Blood samples were collected at specific timepoints for the laboratory evaluation to assess the ApoA-1 level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline. |
| Mean Change From Baseline in Apolipoproteins B (ApoB) at Week 12 | Baseline and Week 12 | Blood samples were collected at specific timepoints for the laboratory evaluation to assess the ApoB level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline. |
| Mean Change From Baseline in Apolipoproteins C3 (ApoC3) at Week 12 | Baseline and Week 12 | Blood samples were collected at specific timepoints for the laboratory evaluation to assess the ApoC3 level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline. |
| Mean Change From Baseline in Fasting Blood Glucose at Week 12 | Baseline and Week 12 | Blood samples were collected at specific timepoints for the laboratory evaluation to assess the fasting glucose level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline. |
| Mean Change From Baseline in Fasting Insulin at Week 12 | Baseline and Week 12 | Blood samples were collected at specific timepoints for the laboratory evaluation to assess the fasting insulin (in micro International units per milliliter \[μIU/mL\]). Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline. |
| Mean Change From Baseline in HOMA Index for Diabetic Participants at Week 12 | Baseline and Week 12 | Blood samples were collected at specific timepoints for the laboratory evaluation; from the results of fasting glucose and insulin, an insulin resistance (IR) was estimated for the nondiabetic participants using the HOMA-IR computer algorithm. A higher HOMA-IR indicates a higher degree of insulin resistance. Participants who were considered as having T2DM were identified as diabetic. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline. |
| Mean Change From Baseline in Glycated Hemoglobin (HbA1c) in Participants With T2DM at Week 12 | Baseline and Week 12 | Blood samples were collected at specific timepoints for the laboratory evaluation to assess the HbA1c. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline. |
| Maximum Plasma Concentration (Cmax) of EDP-305 on Day 1 and Week 12 | Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12) | The Cmax is the maximum observed plasma concentration, which was measured for EDP-305 on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the Pharmacokinetic (PK) Population. |
| Time to Reach Maximum Plasma Concentration (Tmax) of EDP-305 on Day 1 and at Week 12 | Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12) | The Tmax was measured for EDP-305 on Day 1 and at Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population. |
| Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC[Last]) of EDP-305 on Day 1 and at Week 12 | Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12) | AUC(last) is defined as the area under the plasma concentration-time curve from time zero to time the last quantifiable concentration, computed using the linear up/log down trapezoidal rule. AUC(last) was computed for EDP-305 on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population. |
| Mean Change From Baseline in Percentage of Fat in the Liver as Assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) at Week 12 | Baseline and Week 12 | The liver fat percentage was assessed by MRI-PDFF, which is an established method that enables the quantification of fat content in the liver; the value of liver fat is expressed in percentage and ranges from 0 to 100% with higher values representing higher liver fat level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline. |
| Tmax of EP-022571 on Day 1 and at Week 12 | Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12) | The Tmax was measured for EP-022571 (a metabolite of EDP-305) on Day 1 and at Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population. |
| AUC(Last) of EP-022571 on Day 1 and at Week 12 | Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12) | AUC(last) is defined as the area under the plasma concentration-time curve from time zero to time the last quantifiable concentration, computed using the linear up/log down trapezoidal rule. AUC(last) was computed for EP-022571 (a metabolite of EDP-305) on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population. |
| Cmax of EP-022572 on Day 1 and at Week 12 | Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12) | The Cmax is the maximum observed plasma concentration, which was measured for EP-022572 (a metabolite of EDP-305) on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population. |
| Tmax of EP-022572 on Day 1 and at Week 12 | Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12) | The Tmax was measured for EP-022572 (a metabolite of EDP-305) on Day 1 and at Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population. |
| AUC(Last) of EP-022572 on Day 1 and at Week 12 | Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12) | AUC(last) is defined as the area under the plasma concentration-time curve from time zero to time the last quantifiable concentration, computed using the linear up/log down trapezoidal rule. AUC(last) was computed for EP-022572 (a metabolite of EDP-305) on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population. |
| Cmax of EP-022679 on Day 1 and at Week 12 | Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12) | The Cmax is the maximum observed plasma concentration, which was measured for EP-022679 (a metabolite of EDP-305) on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population. |
| Tmax of EP-022679 on Day 1 and at Week 12 | Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12) | The Tmax was measured for EP-022679 (a metabolite of EDP-305) on Day 1 and at Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population. |
| AUC(Last) of EP-022679 on Day 1 and at Week 12 | Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12) | AUC(last) is defined as the area under the plasma concentration-time curve from time zero to time the last quantifiable concentration, computed using the linear up/log down trapezoidal rule. AUC(last) was computed for EP-022679 (a metabolite of EDP-305) on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population. |
| Mean Change From Baseline in Body Weight at Week 12 | Baseline and Week 12 | Body weight was measured at specific timepoints for the participants. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline. |
| Mean Change From Baseline in Waist to Hip (WTH) Ratio at Week 12 | Baseline and Week 12 | The WTH ratio is calculated as the ratio of waist to hip circumference, which was measured at specific timepoints. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline. |
| Mean Change From Baseline in Fibroblast Growth Factor 19 (FGF19) by Nominal Timepoint (Intensive Pharmacodynamic [PD] Samples) at Week 12 | Predose and 2, 6, and 8 hours postdose on Day 1 and Day 84 (Week 12) | Blood samples were collected according to the intensive sampling scheme at specific timepoints to assess the PD marker: FGF19. Baseline refers to the last non-missing predose value collected prior to the most recent dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline. |
| Mean Change From Baseline in FGF19 by Bin Timepoint (Sparse PD Samples) at Week 12 | Predose and two samples postdose (first sample between 1 to 3 hours postdose and second sample 1 hour later than fist sample) on Day 1 and Day 84 (Week 12) | Blood samples were collected according to the sparse sampling scheme at specific timepoints to assess the PD marker: FGF19. Baseline refers to the last non-missing predose value collected prior to the most recent dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline. |
| Mean Change From Baseline in 7a-Hydroxy-4-Cholestene-3-One (C4) by Nominal Timepoint (Intensive PD Samples) at Week 12 | Predose and 2, 6, and 8 hours postdose on Day 1 and Day 84 (Week 12) | Blood samples were collected according to the intensive sampling scheme at specific timepoints to assess the PD marker: C4. Baseline refers to the last non-missing predose value collected prior to the most recent dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline. |
| Mean Change From Baseline in C4 by Bin Timepoint (Sparse PD Samples) at Week 12 | Predose and two samples postdose (first sample between 1 to 3 hours postdose and second sample 1 hour later than fist sample) on Day 1 and Day 84 (Week 12) | Blood samples were collected according to the sparse sampling scheme at specific timepoints to assess the PD marker: C4. Baseline refers to the last non-missing predose value collected prior to the most recent dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline. |
| Mean Change From Baseline in Bile Acid (BA) by Nominal Timepoint (Intensive PD Samples) at Week 12 | Predose and 2, 6, and 8 hours postdose on Day 1 and Day 84 (Week 12) | Blood samples were collected according to the intensive sampling scheme at specific timepoints to assess the PD marker: BA. Baseline refers to the last non-missing predose value collected prior to the most recent dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline. |
| Mean Change From Baseline in BA by Bin Timepoint (Sparse PD Samples) at Week 12 | Predose and two samples postdose (first sample between 1 to 3 hours postdose and second sample 1 hour later than fist sample) on Day 1 and Day 84 (Week 12) | Blood samples were collected according to the sparse sampling scheme at specific timepoints to assess the PD marker: BA. Baseline refers to the last non-missing predose value collected prior to the most recent dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline. |
| Cmax of EP-022571 on Day 1 and at Week 12 | Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12) | The Cmax is the maximum observed plasma concentration, which was measured for EP-022571 (a metabolite of EDP-305) on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population. |
Countries
Canada, France, New Zealand, Puerto Rico, United Kingdom, United States
Participant flow
Pre-assignment details
The Safety or Efficacy Population consisted of all participants who received at least one dose of the study treatment. Out of 134 randomized participants, 2 participants (1 participant each in the EDP-305 2.5 mg and placebo groups) were randomized but not dosed because the participants withdrew and were not included in the Safety and Efficacy Populations.
Participants by arm
| Arm | Count |
|---|---|
| Placebo A matching placebo tablet (EDP-305 1 mg or 2.5 mg) was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. The matching placebo contained all the excipients present in the EDP-305 drug product tablets with the exception of the active drug. | 24 |
| EDP-305 1 mg EDP-305 1 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. | 55 |
| EDP-305 2.5 mg EDP-305 2.5 mg tablet was administered orally once daily in the morning after fasting overnight for a minimum of 8 hours for 12 weeks. | 53 |
| Total | 132 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 12 |
| Overall Study | Lost to Follow-up | 1 | 1 | 1 |
| Overall Study | Participant met Stopping Rules | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 2 | 1 |
Baseline characteristics
| Characteristic | Placebo | EDP-305 1 mg | EDP-305 2.5 mg | Total |
|---|---|---|---|---|
| Age, Customized <65 years | 22 Participants | 52 Participants | 46 Participants | 120 Participants |
| Age, Customized ≥65 years | 2 Participants | 3 Participants | 7 Participants | 12 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 7 Participants | 3 Participants | 11 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Mexican | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not reported | 2 Participants | 2 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Not specified | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 17 Participants | 42 Participants | 47 Participants | 106 Participants |
| Sex: Female, Male Female | 11 Participants | 29 Participants | 29 Participants | 69 Participants |
| Sex: Female, Male Male | 13 Participants | 26 Participants | 24 Participants | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 55 | 0 / 53 |
| other Total, other adverse events | 8 / 24 | 17 / 55 | 32 / 53 |
| serious Total, serious adverse events | 1 / 24 | 1 / 55 | 0 / 53 |
Outcome results
Primary
Mean Change From Baseline (Average) in Alanine Aminotransferase (ALT) at Week 12
Blood samples were collected at specific timepoints for the laboratory evaluation to assess the ALT level. Baseline refers to the average of the screening and the Day 1 values; if either the screening or Day 1 values were missing, the non-missing value was used. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.
Time frame: Baseline and Week 12
Population: Efficacy Population: included all participants who received at least one dose of the study treatment. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure. Only those participants with valid measurements for the outcome measure at the specified time point were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline (Average) in Alanine Aminotransferase (ALT) at Week 12 | -13.85 units per liter (U/L) | Standard Deviation 18.151 |
| EDP-305 1 mg | Mean Change From Baseline (Average) in Alanine Aminotransferase (ALT) at Week 12 | -23.76 units per liter (U/L) | Standard Deviation 28.135 |
| EDP-305 2.5 mg | Mean Change From Baseline (Average) in Alanine Aminotransferase (ALT) at Week 12 | -26.14 units per liter (U/L) | Standard Deviation 33.328 |
p-value: 0.049595% CI: [0.029, 24.891]ANCOVA
p-value: 0.303995% CI: [-5.754, 18.268]ANCOVA
p-value: 0.21395% CI: [-3.615, 16.021]ANCOVA
Secondary
Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC[Last]) of EDP-305 on Day 1 and at Week 12
AUC(last) is defined as the area under the plasma concentration-time curve from time zero to time the last quantifiable concentration, computed using the linear up/log down trapezoidal rule. AUC(last) was computed for EDP-305 on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.
Time frame: Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Population: PK Population: included all participants who received active study drug (EDP-305) and had any measurable plasma concentration of study drug at any timepoint. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure and Number Analyzed = participants who were evaluable for specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC[Last]) of EDP-305 on Day 1 and at Week 12 | Day 1 | 53.6 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 101 |
| Placebo | Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC[Last]) of EDP-305 on Day 1 and at Week 12 | Week 12 | 87.2 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 101 |
| EDP-305 1 mg | Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC[Last]) of EDP-305 on Day 1 and at Week 12 | Day 1 | 129 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 100 |
| EDP-305 1 mg | Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC[Last]) of EDP-305 on Day 1 and at Week 12 | Week 12 | 264 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 100 |
Secondary
AUC(Last) of EP-022571 on Day 1 and at Week 12
AUC(last) is defined as the area under the plasma concentration-time curve from time zero to time the last quantifiable concentration, computed using the linear up/log down trapezoidal rule. AUC(last) was computed for EP-022571 (a metabolite of EDP-305) on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.
Time frame: Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Population: PK Population: included all participants who received active study drug (EDP-305) and had any measurable plasma concentration of study drug at any timepoint. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure and Number Analyzed = participants who were evaluable for specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | AUC(Last) of EP-022571 on Day 1 and at Week 12 | Day 1 | 1.48 h*ng/mL | Geometric Coefficient of Variation 174 |
| Placebo | AUC(Last) of EP-022571 on Day 1 and at Week 12 | Week 12 | 1.41 h*ng/mL | Geometric Coefficient of Variation 187.01 |
| EDP-305 1 mg | AUC(Last) of EP-022571 on Day 1 and at Week 12 | Day 1 | 3.77 h*ng/mL | Geometric Coefficient of Variation 112 |
| EDP-305 1 mg | AUC(Last) of EP-022571 on Day 1 and at Week 12 | Week 12 | 3.81 h*ng/mL | Geometric Coefficient of Variation 121.18 |
Secondary
AUC(Last) of EP-022572 on Day 1 and at Week 12
AUC(last) is defined as the area under the plasma concentration-time curve from time zero to time the last quantifiable concentration, computed using the linear up/log down trapezoidal rule. AUC(last) was computed for EP-022572 (a metabolite of EDP-305) on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.
Time frame: Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Population: PK Population: included all participants who received active study drug (EDP-305) and had any measurable plasma concentration of study drug at any timepoint. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure and Number Analyzed = participants who were evaluable for specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | AUC(Last) of EP-022572 on Day 1 and at Week 12 | Day 1 | 1.06 h*ng/mL | Geometric Coefficient of Variation 220 |
| Placebo | AUC(Last) of EP-022572 on Day 1 and at Week 12 | Week 12 | 1.13 h*ng/mL | Geometric Coefficient of Variation 212 |
| EDP-305 1 mg | AUC(Last) of EP-022572 on Day 1 and at Week 12 | Day 1 | 2.92 h*ng/mL | Geometric Coefficient of Variation 114 |
| EDP-305 1 mg | AUC(Last) of EP-022572 on Day 1 and at Week 12 | Week 12 | 3.19 h*ng/mL | Geometric Coefficient of Variation 116 |
Secondary
AUC(Last) of EP-022679 on Day 1 and at Week 12
AUC(last) is defined as the area under the plasma concentration-time curve from time zero to time the last quantifiable concentration, computed using the linear up/log down trapezoidal rule. AUC(last) was computed for EP-022679 (a metabolite of EDP-305) on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.
Time frame: Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Population: PK Population: included all participants who received active study drug (EDP-305) and had any measurable plasma concentration of study drug at any timepoint. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure and Number Analyzed = participants who were evaluable for specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | AUC(Last) of EP-022679 on Day 1 and at Week 12 | Day 1 | 2.32 h*ng/mL | Geometric Coefficient of Variation 137.54 |
| Placebo | AUC(Last) of EP-022679 on Day 1 and at Week 12 | Week 12 | 7.14 h*ng/mL | Geometric Coefficient of Variation 113 |
| EDP-305 1 mg | AUC(Last) of EP-022679 on Day 1 and at Week 12 | Day 1 | 5.09 h*ng/mL | Geometric Coefficient of Variation 117 |
| EDP-305 1 mg | AUC(Last) of EP-022679 on Day 1 and at Week 12 | Week 12 | 22.5 h*ng/mL | Geometric Coefficient of Variation 104 |
Secondary
Cmax of EP-022571 on Day 1 and at Week 12
The Cmax is the maximum observed plasma concentration, which was measured for EP-022571 (a metabolite of EDP-305) on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.
Time frame: Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Population: PK Population: included all participants who received active study drug (EDP-305) and had any measurable plasma concentration of study drug at any timepoint. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure and Number Analyzed = participants who were evaluable for specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Cmax of EP-022571 on Day 1 and at Week 12 | Day 1 | 0.324 ng/mL | Geometric Coefficient of Variation 983 |
| Placebo | Cmax of EP-022571 on Day 1 and at Week 12 | Week 12 | 0.296 ng/mL | Geometric Coefficient of Variation 1549 |
| EDP-305 1 mg | Cmax of EP-022571 on Day 1 and at Week 12 | Day 1 | 0.833 ng/mL | Geometric Coefficient of Variation 177 |
| EDP-305 1 mg | Cmax of EP-022571 on Day 1 and at Week 12 | Week 12 | 0.787 ng/mL | Geometric Coefficient of Variation 233 |
Secondary
Cmax of EP-022572 on Day 1 and at Week 12
The Cmax is the maximum observed plasma concentration, which was measured for EP-022572 (a metabolite of EDP-305) on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.
Time frame: Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Population: PK Population: included all participants who received active study drug (EDP-305) and had any measurable plasma concentration of study drug at any timepoint. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure and Number Analyzed = participants who were evaluable for specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Cmax of EP-022572 on Day 1 and at Week 12 | Day 1 | 0.234 ng/mL | Geometric Coefficient of Variation 1942 |
| Placebo | Cmax of EP-022572 on Day 1 and at Week 12 | Week 12 | 0.214 ng/mL | Geometric Coefficient of Variation 2863 |
| EDP-305 1 mg | Cmax of EP-022572 on Day 1 and at Week 12 | Day 1 | 0.571 ng/mL | Geometric Coefficient of Variation 212 |
| EDP-305 1 mg | Cmax of EP-022572 on Day 1 and at Week 12 | Week 12 | 0.556 ng/mL | Geometric Coefficient of Variation 212 |
Secondary
Cmax of EP-022679 on Day 1 and at Week 12
The Cmax is the maximum observed plasma concentration, which was measured for EP-022679 (a metabolite of EDP-305) on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.
Time frame: Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Population: PK Population: included all participants who received active study drug (EDP-305) and had any measurable plasma concentration of study drug at any timepoint. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure and Number Analyzed = participants who were evaluable for specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Cmax of EP-022679 on Day 1 and at Week 12 | Day 1 | 0.574 ng/mL | Geometric Coefficient of Variation 321 |
| Placebo | Cmax of EP-022679 on Day 1 and at Week 12 | Week 12 | 1.41 ng/mL | Geometric Coefficient of Variation 117 |
| EDP-305 1 mg | Cmax of EP-022679 on Day 1 and at Week 12 | Day 1 | 1.28 ng/mL | Geometric Coefficient of Variation 167 |
| EDP-305 1 mg | Cmax of EP-022679 on Day 1 and at Week 12 | Week 12 | 3.85 ng/mL | Geometric Coefficient of Variation 122 |
Secondary
Maximum Plasma Concentration (Cmax) of EDP-305 on Day 1 and Week 12
The Cmax is the maximum observed plasma concentration, which was measured for EDP-305 on Day 1 and Week 12 for the samples collected according to the intensive sampling scheme for the participants in the Pharmacokinetic (PK) Population.
Time frame: Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Population: PK Population: included all participants who received active study drug (EDP-305) and had any measurable plasma concentration of study drug at any timepoint. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure and Number Analyzed = participants who were evaluable for specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Plasma Concentration (Cmax) of EDP-305 on Day 1 and Week 12 | Day 1 | 11.1 ng/mL | Geometric Coefficient of Variation 105 |
| Placebo | Maximum Plasma Concentration (Cmax) of EDP-305 on Day 1 and Week 12 | Week 12 | 15.9 ng/mL | Geometric Coefficient of Variation 105 |
| EDP-305 1 mg | Maximum Plasma Concentration (Cmax) of EDP-305 on Day 1 and Week 12 | Day 1 | 25.1 ng/mL | Geometric Coefficient of Variation 101 |
| EDP-305 1 mg | Maximum Plasma Concentration (Cmax) of EDP-305 on Day 1 and Week 12 | Week 12 | 41.1 ng/mL | Geometric Coefficient of Variation 101 |
Secondary
Mean Change From Baseline in 7a-Hydroxy-4-Cholestene-3-One (C4) by Nominal Timepoint (Intensive PD Samples) at Week 12
Blood samples were collected according to the intensive sampling scheme at specific timepoints to assess the PD marker: C4. Baseline refers to the last non-missing predose value collected prior to the most recent dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.
Time frame: Predose and 2, 6, and 8 hours postdose on Day 1 and Day 84 (Week 12)
Population: Efficacy Population: included all participants who received at least one dose of the study treatment. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure. Only those participants with valid measurements for the outcome measure at the specified time point were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in 7a-Hydroxy-4-Cholestene-3-One (C4) by Nominal Timepoint (Intensive PD Samples) at Week 12 | -9.484 ng/mL | Standard Deviation 20.6295 |
| EDP-305 1 mg | Mean Change From Baseline in 7a-Hydroxy-4-Cholestene-3-One (C4) by Nominal Timepoint (Intensive PD Samples) at Week 12 | -36.783 ng/mL | Standard Deviation 24.656 |
| EDP-305 2.5 mg | Mean Change From Baseline in 7a-Hydroxy-4-Cholestene-3-One (C4) by Nominal Timepoint (Intensive PD Samples) at Week 12 | -40.567 ng/mL | Standard Deviation 20.926 |
p-value: <0.000195% CI: [17.984, 48.998]ANCOVA
p-value: <0.000195% CI: [15.802, 45.825]ANCOVA
p-value: 0.675795% CI: [-9.946, 15.3]ANCOVA
Secondary
Mean Change From Baseline in Adiponectin at Week 12
Blood samples were collected at specific timepoints for the laboratory evaluation to assess the adiponectin level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.
Time frame: Baseline and Week 12
Population: Efficacy Population: included all participants who received at least one dose of the study treatment. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure. Only those participants with valid measurements for the outcome measure at the specified time point were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Adiponectin at Week 12 | 319.16 nanogram per milliliter (ng/mL) | Standard Deviation 689.387 |
| EDP-305 1 mg | Mean Change From Baseline in Adiponectin at Week 12 | 17.94 nanogram per milliliter (ng/mL) | Standard Deviation 828.494 |
| EDP-305 2.5 mg | Mean Change From Baseline in Adiponectin at Week 12 | 522.00 nanogram per milliliter (ng/mL) | Standard Deviation 2649.701 |
p-value: 0.914395% CI: [-901.574, 1005.32]ANCOVA
p-value: 0.371895% CI: [-489.519, 1297.854]ANCOVA
p-value: 0.346695% CI: [-1091.308, 386.719]ANCOVA
Secondary
Mean Change From Baseline in Apolipoproteins A1 (ApoA-1) at Week 12
Blood samples were collected at specific timepoints for the laboratory evaluation to assess the ApoA-1 level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.
Time frame: Baseline and Week 12
Population: Efficacy Population: included all participants who received at least one dose of the study treatment. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure. Only those participants with valid measurements for the outcome measure at the specified time point were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Apolipoproteins A1 (ApoA-1) at Week 12 | -0.074 proteins*10^9/L | Standard Deviation 0.1514 |
| EDP-305 1 mg | Mean Change From Baseline in Apolipoproteins A1 (ApoA-1) at Week 12 | -0.107 proteins*10^9/L | Standard Deviation 0.1671 |
| EDP-305 2.5 mg | Mean Change From Baseline in Apolipoproteins A1 (ApoA-1) at Week 12 | -0.226 proteins*10^9/L | Standard Deviation 0.2197 |
p-value: 0.000395% CI: [0.081, 0.264]ANCOVA
p-value: 0.568595% CI: [-0.062, 0.113]ANCOVA
p-value: <0.000195% CI: [0.075, 0.219]ANCOVA
Secondary
Mean Change From Baseline in Apolipoproteins B (ApoB) at Week 12
Blood samples were collected at specific timepoints for the laboratory evaluation to assess the ApoB level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.
Time frame: Baseline and Week 12
Population: Efficacy Population: included all participants who received at least one dose of the study treatment. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure. Only those participants with valid measurements for the outcome measure at the specified time point were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Apolipoproteins B (ApoB) at Week 12 | -0.028 proteins*10^9/L | Standard Deviation 0.1687 |
| EDP-305 1 mg | Mean Change From Baseline in Apolipoproteins B (ApoB) at Week 12 | 0.040 proteins*10^9/L | Standard Deviation 0.1781 |
| EDP-305 2.5 mg | Mean Change From Baseline in Apolipoproteins B (ApoB) at Week 12 | 0.099 proteins*10^9/L | Standard Deviation 0.2898 |
p-value: 0.028295% CI: [-0.252, -0.015]ANCOVA
p-value: 0.241295% CI: [-0.182, 0.046]ANCOVA
p-value: 0.164995% CI: [-0.158, 0.027]ANCOVA
Secondary
Mean Change From Baseline in Apolipoproteins C3 (ApoC3) at Week 12
Blood samples were collected at specific timepoints for the laboratory evaluation to assess the ApoC3 level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.
Time frame: Baseline and Week 12
Population: Efficacy Population: included all participants who received at least one dose of the study treatment. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure. Only those participants with valid measurements for the outcome measure at the specified time point were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Apolipoproteins C3 (ApoC3) at Week 12 | -0.0094 proteins*10^9/L | Standard Deviation 0.04388 |
| EDP-305 1 mg | Mean Change From Baseline in Apolipoproteins C3 (ApoC3) at Week 12 | -0.0167 proteins*10^9/L | Standard Deviation 0.03918 |
| EDP-305 2.5 mg | Mean Change From Baseline in Apolipoproteins C3 (ApoC3) at Week 12 | -0.0122 proteins*10^9/L | Standard Deviation 0.05721 |
p-value: 0.435795% CI: [-0.014, 0.032]ANCOVA
p-value: 0.898995% CI: [-0.021, 0.023]ANCOVA
p-value: 0.41295% CI: [-0.011, 0.026]ANCOVA
Secondary
Mean Change From Baseline in Aspartate Aminotransferase to Platelet Ratio Index (APRI) at Week 12
Blood samples were collected at specific timepoints for the laboratory evaluation to assess the aspartate aminotransferase (AST) level and platelet count. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. The APRI score (AST to platelet ratio index) is an index comprised of biochemical values and is used to determine the degree of hepatic fibrosis. APRI is calculated from the level of AST measured in a blood test (international units per liter \[IU/L\]) and platelet count (10\^9/L) according to the following formula: APRI = (\[AST value in IU/L / upper limit of the normal range of AST\] / \[platelet count in 10\^9/L\]) × 100. In general, APRI scores range from 0 to \>2.0, where scores \<0.5 indicate no significant fibrosis, scores \>1.5 indicate significant fibrosis, and scores \>2.0 have been shown to be best correlated with the presence of cirrhosis. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.
Time frame: Baseline and Week 12
Population: Efficacy Population: included all participants who received at least one dose of the study treatment. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure. Only those participants with valid measurements for the outcome measure at the specified time point were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Aspartate Aminotransferase to Platelet Ratio Index (APRI) at Week 12 | -0.180 ratio | Standard Deviation 0.3462 |
| EDP-305 1 mg | Mean Change From Baseline in Aspartate Aminotransferase to Platelet Ratio Index (APRI) at Week 12 | -0.107 ratio | Standard Deviation 0.3396 |
| EDP-305 2.5 mg | Mean Change From Baseline in Aspartate Aminotransferase to Platelet Ratio Index (APRI) at Week 12 | -0.194 ratio | Standard Deviation 0.3533 |
p-value: 0.275695% CI: [-0.062, 0.214]ANCOVA
p-value: 0.968695% CI: [-0.136, 0.131]ANCOVA
p-value: 0.140695% CI: [-0.026, 0.184]ANCOVA
Secondary
Mean Change From Baseline in BA by Bin Timepoint (Sparse PD Samples) at Week 12
Blood samples were collected according to the sparse sampling scheme at specific timepoints to assess the PD marker: BA. Baseline refers to the last non-missing predose value collected prior to the most recent dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.
Time frame: Predose and two samples postdose (first sample between 1 to 3 hours postdose and second sample 1 hour later than fist sample) on Day 1 and Day 84 (Week 12)
Population: Efficacy Population: included all participants who received at least one dose of the study treatment. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure. Only those participants with valid measurements for the outcome measure at the specified time point were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in BA by Bin Timepoint (Sparse PD Samples) at Week 12 | 0.77 μmol/L | Standard Deviation 5.789 |
| EDP-305 1 mg | Mean Change From Baseline in BA by Bin Timepoint (Sparse PD Samples) at Week 12 | -0.11 μmol/L | Standard Deviation 2.783 |
| EDP-305 2.5 mg | Mean Change From Baseline in BA by Bin Timepoint (Sparse PD Samples) at Week 12 | 0.74 μmol/L | Standard Deviation 4.091 |
p-value: 0.991395% CI: [-3.491, 3.53]ANCOVA
p-value: 0.55395% CI: [-2.323, 4.314]ANCOVA
p-value: 0.472995% CI: [-3.665, 1.713]ANCOVA
Secondary
Mean Change From Baseline in Bile Acid (BA) by Nominal Timepoint (Intensive PD Samples) at Week 12
Blood samples were collected according to the intensive sampling scheme at specific timepoints to assess the PD marker: BA. Baseline refers to the last non-missing predose value collected prior to the most recent dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.
Time frame: Predose and 2, 6, and 8 hours postdose on Day 1 and Day 84 (Week 12)
Population: Efficacy Population: included all participants who received at least one dose of the study treatment. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure. Only those participants with valid measurements for the outcome measure at the specified time point were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Bile Acid (BA) by Nominal Timepoint (Intensive PD Samples) at Week 12 | 4.47 micromoles per liter (μmol/L) | Standard Deviation 3.668 |
| EDP-305 1 mg | Mean Change From Baseline in Bile Acid (BA) by Nominal Timepoint (Intensive PD Samples) at Week 12 | 2.16 micromoles per liter (μmol/L) | Standard Deviation 5.507 |
| EDP-305 2.5 mg | Mean Change From Baseline in Bile Acid (BA) by Nominal Timepoint (Intensive PD Samples) at Week 12 | 0.14 micromoles per liter (μmol/L) | Standard Deviation 3.125 |
p-value: 0.055795% CI: [-0.108, 8.756]ANCOVA
p-value: 0.286795% CI: [-1.955, 6.566]ANCOVA
p-value: 0.243795% CI: [-1.39, 5.429]ANCOVA
Secondary
Mean Change From Baseline in Body Weight at Week 12
Body weight was measured at specific timepoints for the participants. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.
Time frame: Baseline and Week 12
Population: Efficacy Population: included all participants who received at least one dose of the study treatment. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure. Only those participants with valid measurements for the outcome measure at the specified time point were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Body Weight at Week 12 | -0.877 kilograms (kg) | Standard Deviation 2.81 |
| EDP-305 1 mg | Mean Change From Baseline in Body Weight at Week 12 | -1.440 kilograms (kg) | Standard Deviation 2.7984 |
| EDP-305 2.5 mg | Mean Change From Baseline in Body Weight at Week 12 | -2.114 kilograms (kg) | Standard Deviation 3.2829 |
p-value: 0.11295% CI: [-0.322, 3.034]ANCOVA
p-value: 0.422995% CI: [-0.947, 2.24]ANCOVA
p-value: 0.276495% CI: [-0.577, 1.996]ANCOVA
Secondary
Mean Change From Baseline in C4 by Bin Timepoint (Sparse PD Samples) at Week 12
Blood samples were collected according to the sparse sampling scheme at specific timepoints to assess the PD marker: C4. Baseline refers to the last non-missing predose value collected prior to the most recent dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.
Time frame: Predose and two samples postdose (first sample between 1 to 3 hours postdose and second sample 1 hour later than fist sample) on Day 1 and Day 84 (Week 12)
Population: Efficacy Population: included all participants who received at least one dose of the study treatment. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure. Only those participants with valid measurements for the outcome measure at the specified time point were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in C4 by Bin Timepoint (Sparse PD Samples) at Week 12 | -5.242 ng/mL | Standard Deviation 30.5321 |
| EDP-305 1 mg | Mean Change From Baseline in C4 by Bin Timepoint (Sparse PD Samples) at Week 12 | -13.500 ng/mL | Standard Deviation 26.2458 |
| EDP-305 2.5 mg | Mean Change From Baseline in C4 by Bin Timepoint (Sparse PD Samples) at Week 12 | -23.773 ng/mL | Standard Deviation 20.7045 |
p-value: 0.013495% CI: [4.533, 38.067]ANCOVA
p-value: 0.468695% CI: [-10.116, 21.811]ANCOVA
p-value: 0.018195% CI: [2.699, 28.206]ANCOVA
Secondary
Mean Change From Baseline in Fasting Blood Glucose at Week 12
Blood samples were collected at specific timepoints for the laboratory evaluation to assess the fasting glucose level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.
Time frame: Baseline and Week 12
Population: Efficacy Population: included all participants who received at least one dose of the study treatment. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure. Only those participants with valid measurements for the outcome measure at the specified time point were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Fasting Blood Glucose at Week 12 | -0.11 mmol/L | Standard Deviation 2.13 |
| EDP-305 1 mg | Mean Change From Baseline in Fasting Blood Glucose at Week 12 | 0.48 mmol/L | Standard Deviation 1.847 |
| EDP-305 2.5 mg | Mean Change From Baseline in Fasting Blood Glucose at Week 12 | 1.68 mmol/L | Standard Deviation 3.396 |
p-value: 0.013495% CI: [-3.095, -0.368]ANCOVA
p-value: 0.626395% CI: [-1.656, 1.001]ANCOVA
p-value: 0.011595% CI: [-2.487, -0.322]ANCOVA
Secondary
Mean Change From Baseline in Fasting Insulin at Week 12
Blood samples were collected at specific timepoints for the laboratory evaluation to assess the fasting insulin (in micro International units per milliliter \[μIU/mL\]). Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.
Time frame: Baseline and Week 12
Population: Efficacy Population: included all participants who received at least one dose of the study treatment. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure. Only those participants with valid measurements for the outcome measure at the specified time point were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Fasting Insulin at Week 12 | -0.688 μIU/mL | Standard Deviation 9.2808 |
| EDP-305 1 mg | Mean Change From Baseline in Fasting Insulin at Week 12 | 2.528 μIU/mL | Standard Deviation 14.6947 |
| EDP-305 2.5 mg | Mean Change From Baseline in Fasting Insulin at Week 12 | -5.635 μIU/mL | Standard Deviation 52.7637 |
p-value: 0.460895% CI: [-13.7, 6.253]ANCOVA
p-value: 0.623895% CI: [-11.962, 7.207]ANCOVA
p-value: 0.736795% CI: [-9.268, 6.576]ANCOVA
Secondary
Mean Change From Baseline in FGF19 by Bin Timepoint (Sparse PD Samples) at Week 12
Blood samples were collected according to the sparse sampling scheme at specific timepoints to assess the PD marker: FGF19. Baseline refers to the last non-missing predose value collected prior to the most recent dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.
Time frame: Predose and two samples postdose (first sample between 1 to 3 hours postdose and second sample 1 hour later than fist sample) on Day 1 and Day 84 (Week 12)
Population: Efficacy Population: included all participants who received at least one dose of the study treatment. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure. Only those participants with valid measurements for the outcome measure at the specified time point were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in FGF19 by Bin Timepoint (Sparse PD Samples) at Week 12 | 33.51 ng/L | Standard Deviation 155.744 |
| EDP-305 1 mg | Mean Change From Baseline in FGF19 by Bin Timepoint (Sparse PD Samples) at Week 12 | 46.04 ng/L | Standard Deviation 88.662 |
| EDP-305 2.5 mg | Mean Change From Baseline in FGF19 by Bin Timepoint (Sparse PD Samples) at Week 12 | 813.29 ng/L | Standard Deviation 3200.567 |
p-value: 0.298595% CI: [-2183.92, 677.614]ANCOVA
p-value: 0.841395% CI: [-1236.689, 1514.902]ANCOVA
p-value: 0.116895% CI: [-2011.705, 227.186]ANCOVA
Secondary
Mean Change From Baseline in Fibroblast Growth Factor 19 (FGF19) by Nominal Timepoint (Intensive Pharmacodynamic [PD] Samples) at Week 12
Blood samples were collected according to the intensive sampling scheme at specific timepoints to assess the PD marker: FGF19. Baseline refers to the last non-missing predose value collected prior to the most recent dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.
Time frame: Predose and 2, 6, and 8 hours postdose on Day 1 and Day 84 (Week 12)
Population: Efficacy Population: included all participants who received at least one dose of the study treatment. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure. Only those participants with valid measurements for the outcome measure at the specified time point were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Fibroblast Growth Factor 19 (FGF19) by Nominal Timepoint (Intensive Pharmacodynamic [PD] Samples) at Week 12 | 159.98 nanogram per liter (ng/L) | Standard Deviation 165.245 |
| EDP-305 1 mg | Mean Change From Baseline in Fibroblast Growth Factor 19 (FGF19) by Nominal Timepoint (Intensive Pharmacodynamic [PD] Samples) at Week 12 | 410.00 nanogram per liter (ng/L) | Standard Deviation 260.223 |
| EDP-305 2.5 mg | Mean Change From Baseline in Fibroblast Growth Factor 19 (FGF19) by Nominal Timepoint (Intensive Pharmacodynamic [PD] Samples) at Week 12 | 607.12 nanogram per liter (ng/L) | Standard Deviation 891.553 |
p-value: 0.701495% CI: [-1098.454, 740.88]ANCOVA
p-value: 0.90795% CI: [-830.934, 935.547]ANCOVA
p-value: 0.53695% CI: [-967.273, 505.086]ANCOVA
Secondary
Mean Change From Baseline in Glycated Hemoglobin (HbA1c) in Participants With T2DM at Week 12
Blood samples were collected at specific timepoints for the laboratory evaluation to assess the HbA1c. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.
Time frame: Baseline and Week 12
Population: Efficacy Population: included all participants who received at least one dose of the study treatment. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure. Only those participants with valid measurements for the outcome measure at the specified time point were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Glycated Hemoglobin (HbA1c) in Participants With T2DM at Week 12 | 0.31 percentage of glycated hemoglobin | Standard Deviation 0.685 |
| EDP-305 1 mg | Mean Change From Baseline in Glycated Hemoglobin (HbA1c) in Participants With T2DM at Week 12 | 0.21 percentage of glycated hemoglobin | Standard Deviation 0.776 |
| EDP-305 2.5 mg | Mean Change From Baseline in Glycated Hemoglobin (HbA1c) in Participants With T2DM at Week 12 | 0.76 percentage of glycated hemoglobin | Standard Deviation 0.963 |
p-value: 0.081195% CI: [-0.978, 0.058]ANCOVA
p-value: 0.631295% CI: [-0.367, 0.601]ANCOVA
p-value: 0.009995% CI: [-1.011, -0.143]ANCOVA
Secondary
Mean Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12
Blood samples were collected at specific timepoints for the laboratory evaluation to assess the HDL-C level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.
Time frame: Baseline and Week 12
Population: Efficacy Population: included all participants who received at least one dose of the study treatment. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure. Only those participants with valid measurements for the outcome measure at the specified time point were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12 | 0.008 mmol/L | Standard Deviation 0.1279 |
| EDP-305 1 mg | Mean Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12 | -0.058 mmol/L | Standard Deviation 0.167 |
| EDP-305 2.5 mg | Mean Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12 | -0.210 mmol/L | Standard Deviation 0.2708 |
p-value: <0.000195% CI: [0.11, 0.311]ANCOVA
p-value: 0.34895% CI: [-0.051, 0.143]ANCOVA
p-value: <0.000195% CI: [0.085, 0.243]ANCOVA
Secondary
Mean Change From Baseline in HOMA Index for Diabetic Participants at Week 12
Blood samples were collected at specific timepoints for the laboratory evaluation; from the results of fasting glucose and insulin, an insulin resistance (IR) was estimated for the nondiabetic participants using the HOMA-IR computer algorithm. A higher HOMA-IR indicates a higher degree of insulin resistance. Participants who were considered as having T2DM were identified as diabetic. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.
Time frame: Baseline and Week 12
Population: Efficacy Population: included all participants who received at least one dose of the study treatment. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure. Only those participants with valid measurements for the outcome measure at the specified time point were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in HOMA Index for Diabetic Participants at Week 12 | -0.493 units on a scale | Standard Deviation 6.2624 |
| EDP-305 1 mg | Mean Change From Baseline in HOMA Index for Diabetic Participants at Week 12 | 2.088 units on a scale | Standard Deviation 6.6114 |
| EDP-305 2.5 mg | Mean Change From Baseline in HOMA Index for Diabetic Participants at Week 12 | 5.059 units on a scale | Standard Deviation 15.0113 |
p-value: 0.063995% CI: [-12.171, 0.351]ANCOVA
p-value: 0.488495% CI: [-7.971, 3.843]ANCOVA
p-value: 0.153295% CI: [-9.156, 1.464]ANCOVA
Secondary
Mean Change From Baseline in Homeostasis Model Assessment (HOMA) Index for Nondiabetic Participants at Week 12
Blood samples were collected at specific timepoints for the laboratory evaluation; from the results of fasting glucose and insulin, an insulin resistance (IR) was estimated for the nondiabetic participants using the HOMA-IR computer algorithm. A higher HOMA-IR indicates a higher degree of insulin resistance. Participants who were not considered as having type 2 diabetes mellitus (T2DM) were identified as nondiabetic. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.
Time frame: Baseline and Week 12
Population: Efficacy Population: included all participants who received at least one dose of the study treatment. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure. Only those participants with valid measurements for the outcome measure at the specified time point were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Homeostasis Model Assessment (HOMA) Index for Nondiabetic Participants at Week 12 | 0.587 units on a scale | Standard Deviation 2.0088 |
| EDP-305 1 mg | Mean Change From Baseline in Homeostasis Model Assessment (HOMA) Index for Nondiabetic Participants at Week 12 | 0.192 units on a scale | Standard Deviation 2.718 |
| EDP-305 2.5 mg | Mean Change From Baseline in Homeostasis Model Assessment (HOMA) Index for Nondiabetic Participants at Week 12 | -6.474 units on a scale | Standard Deviation 24.9369 |
p-value: 0.830295% CI: [-4.287, 3.474]ANCOVA
p-value: 0.505395% CI: [-5.192, 2.632]ANCOVA
p-value: 0.47695% CI: [-1.62, 3.366]ANCOVA
Secondary
Mean Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
Blood samples were collected at specific timepoints for the laboratory evaluation to assess the LDL-C level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.
Time frame: Baseline and Week 12
Population: Efficacy Population: included all participants who received at least one dose of the study treatment. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure. Only those participants with valid measurements for the outcome measure at the specified time point were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | -0.112 mmol/L | Standard Deviation 0.6431 |
| EDP-305 1 mg | Mean Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | 0.129 mmol/L | Standard Deviation 0.5099 |
| EDP-305 2.5 mg | Mean Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | 0.151 mmol/L | Standard Deviation 0.8157 |
p-value: 0.089795% CI: [-0.645, 0.047]ANCOVA
p-value: 0.141195% CI: [-0.586, 0.085]ANCOVA
p-value: 0.73395% CI: [-0.326, 0.23]ANCOVA
Secondary
Mean Change From Baseline in Percentage of Fat in the Liver as Assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) at Week 12
The liver fat percentage was assessed by MRI-PDFF, which is an established method that enables the quantification of fat content in the liver; the value of liver fat is expressed in percentage and ranges from 0 to 100% with higher values representing higher liver fat level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.
Time frame: Baseline and Week 12
Population: Efficacy Population: included all participants who received at least one dose of the study treatment. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure. Only those participants with valid measurements for the outcome measure at the specified time point were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Percentage of Fat in the Liver as Assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) at Week 12 | -2.842 percentage of fat | Standard Deviation 4.4687 |
| EDP-305 1 mg | Mean Change From Baseline in Percentage of Fat in the Liver as Assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) at Week 12 | -3.759 percentage of fat | Standard Deviation 5.16 |
| EDP-305 2.5 mg | Mean Change From Baseline in Percentage of Fat in the Liver as Assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) at Week 12 | -6.428 percentage of fat | Standard Deviation 7.2586 |
p-value: 0.000995% CI: [1.98, 7.455]ANCOVA
p-value: 0.494695% CI: [-1.766, 3.635]ANCOVA
p-value: 0.000595% CI: [1.708, 5.858]ANCOVA
Secondary
Mean Change From Baseline in Total Cholesterol at Week 12
Blood samples were collected at specific timepoints for the laboratory evaluation to assess the total cholesterol level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.
Time frame: Baseline and Week 12
Population: Efficacy Population: included all participants who received at least one dose of the study treatment. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure. Only those participants with valid measurements for the outcome measure at the specified time point were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Total Cholesterol at Week 12 | -0.175 mmol/L | Standard Deviation 0.6879 |
| EDP-305 1 mg | Mean Change From Baseline in Total Cholesterol at Week 12 | 0.046 mmol/L | Standard Deviation 0.6697 |
| EDP-305 2.5 mg | Mean Change From Baseline in Total Cholesterol at Week 12 | -0.003 mmol/L | Standard Deviation 1.0046 |
p-value: 0.387595% CI: [-0.613, 0.24]ANCOVA
p-value: 0.233195% CI: [-0.657, 0.162]ANCOVA
p-value: 0.716495% CI: [-0.272, 0.395]ANCOVA
Secondary
Mean Change From Baseline in Triglycerides (TG) at Week 12
Blood samples were collected at specific timepoints for the laboratory evaluation to assess the TG level. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.
Time frame: Baseline and Week 12
Population: Efficacy Population: included all participants who received at least one dose of the study treatment. Here Overall Number of Participants Analyzed= participants evaluable for this outcome measure. Only those participants with valid measurements for the outcome measure at the specified time point were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Triglycerides (TG) at Week 12 | -0.151 millimoles per liter (mmol/L) | Standard Deviation 0.8529 |
| EDP-305 1 mg | Mean Change From Baseline in Triglycerides (TG) at Week 12 | -0.366 millimoles per liter (mmol/L) | Standard Deviation 1.5858 |
| EDP-305 2.5 mg | Mean Change From Baseline in Triglycerides (TG) at Week 12 | 0.129 millimoles per liter (mmol/L) | Standard Deviation 1.1088 |
p-value: 0.61395% CI: [-0.613, 0.363]ANCOVA
p-value: 0.836695% CI: [-0.521, 0.423]ANCOVA
p-value: 0.701595% CI: [-0.466, 0.315]ANCOVA
Secondary
Mean Change From Baseline in Waist to Hip (WTH) Ratio at Week 12
The WTH ratio is calculated as the ratio of waist to hip circumference, which was measured at specific timepoints. Baseline refers to the last non-missing value collected prior to the first dose of study treatment. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.
Time frame: Baseline and Week 12
Population: Efficacy Population: included all participants who received at least one dose of the study treatment. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure. Only those participants with valid measurements for the outcome measure at the specified time point were reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Waist to Hip (WTH) Ratio at Week 12 | 0.013 ratio | Standard Deviation 0.0729 |
| EDP-305 1 mg | Mean Change From Baseline in Waist to Hip (WTH) Ratio at Week 12 | -0.007 ratio | Standard Deviation 0.0477 |
| EDP-305 2.5 mg | Mean Change From Baseline in Waist to Hip (WTH) Ratio at Week 12 | 0.014 ratio | Standard Deviation 0.0509 |
p-value: 0.560695% CI: [-0.02, 0.037]ANCOVA
p-value: 0.100295% CI: [-0.004, 0.05]ANCOVA
p-value: 0.200295% CI: [-0.036, 0.008]ANCOVA
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) of EDP-305 on Day 1 and at Week 12
The Tmax was measured for EDP-305 on Day 1 and at Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.
Time frame: Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Population: PK Population: included all participants who received active study drug (EDP-305) and had any measurable plasma concentration of study drug at any timepoint. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure and Number Analyzed = participants who were evaluable for specified category.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Time to Reach Maximum Plasma Concentration (Tmax) of EDP-305 on Day 1 and at Week 12 | Day 1 | 6.00 hours (h) |
| Placebo | Time to Reach Maximum Plasma Concentration (Tmax) of EDP-305 on Day 1 and at Week 12 | Week 12 | 6.00 hours (h) |
| EDP-305 1 mg | Time to Reach Maximum Plasma Concentration (Tmax) of EDP-305 on Day 1 and at Week 12 | Week 12 | 6.00 hours (h) |
| EDP-305 1 mg | Time to Reach Maximum Plasma Concentration (Tmax) of EDP-305 on Day 1 and at Week 12 | Day 1 | 6.00 hours (h) |
Secondary
Tmax of EP-022571 on Day 1 and at Week 12
The Tmax was measured for EP-022571 (a metabolite of EDP-305) on Day 1 and at Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.
Time frame: Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Population: PK Population: included all participants who received active study drug (EDP-305) and had any measurable plasma concentration of study drug at any timepoint. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure and Number Analyzed = participants who were evaluable for specified category.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Tmax of EP-022571 on Day 1 and at Week 12 | Day 1 | 6.00 h |
| Placebo | Tmax of EP-022571 on Day 1 and at Week 12 | Week 12 | 6.00 h |
| EDP-305 1 mg | Tmax of EP-022571 on Day 1 and at Week 12 | Day 1 | 6.00 h |
| EDP-305 1 mg | Tmax of EP-022571 on Day 1 and at Week 12 | Week 12 | 6.00 h |
Secondary
Tmax of EP-022572 on Day 1 and at Week 12
The Tmax was measured for EP-022572 (a metabolite of EDP-305) on Day 1 and at Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.
Time frame: Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Population: PK Population: included all participants who received active study drug (EDP-305) and had any measurable plasma concentration of study drug at any timepoint. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure and Number Analyzed = participants who were evaluable for specified category.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Tmax of EP-022572 on Day 1 and at Week 12 | Week 12 | 6.00 h |
| Placebo | Tmax of EP-022572 on Day 1 and at Week 12 | Day 1 | 6.00 h |
| EDP-305 1 mg | Tmax of EP-022572 on Day 1 and at Week 12 | Day 1 | 6.00 h |
| EDP-305 1 mg | Tmax of EP-022572 on Day 1 and at Week 12 | Week 12 | 2.05 h |
Secondary
Tmax of EP-022679 on Day 1 and at Week 12
The Tmax was measured for EP-022679 (a metabolite of EDP-305) on Day 1 and at Week 12 for the samples collected according to the intensive sampling scheme for the participants in the PK Population.
Time frame: Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12)
Population: PK Population: included all participants who received active study drug (EDP-305) and had any measurable plasma concentration of study drug at any timepoint. Here Overall Number of Participants Analyzed = participants evaluable for this outcome measure and Number Analyzed = participants who were evaluable for specified category.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Tmax of EP-022679 on Day 1 and at Week 12 | Week 12 | 6.03 h |
| Placebo | Tmax of EP-022679 on Day 1 and at Week 12 | Day 1 | 8.00 h |
| EDP-305 1 mg | Tmax of EP-022679 on Day 1 and at Week 12 | Week 12 | 6.00 h |
| EDP-305 1 mg | Tmax of EP-022679 on Day 1 and at Week 12 | Day 1 | 8.00 h |